Drug & supplement interaction

Ergot + Trofinetide

Trofinetide brand name: Daybue.

Moderate Interaction
The bottom line Moderate

Ergot has a moderate interaction with Trofinetide. Ergotamine, a constituent of ergot, is a substrate of cytochrome P450 3A4 (CYP3A4).

Read the full interaction report
SeverityModerate
LikelihoodPossible
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Ergot and Trofinetide

Here is the interaction we found between these two, with the evidence behind it.

Moderate

CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS

Why this applies to Trofinetide

Trofinetide falls under CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS — the group Ergot interacts with.

Ergotamine, a constituent of ergot, is a substrate of cytochrome P450 3A4 (CYP3A4). Theoretically, drugs that inhibit CYP3A4 might increase the risk of ergot toxicity. Some of these drugs include amiodarone (Cordarone), clarithromycin (Biaxin), diltiazem (Cardizem), erythromycin (E-mycin, Erythrocin), indinavir (Crixivan), ritonavir (Norvir), saquinavir (Fortovase, Invirase), and many others.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the setup: your body clears ergot's active chemical (ergotamine) partly through a liver enzyme called CYP3A4. If something slows that enzyme down, ergot can build up and cause ergot toxicity (things like intense blood vessel narrowing, cold or tingling hands and feet, headache, and in serious cases reduced blood flow to the limbs). So the real question is whether trofinetide (Daybue) blocks that enzyme.

Trofinetide is not a strong known CYP3A4 blocker, so this particular concern doesn't clearly point at Daybue, and the evidence here is only theoretical and anecdotal. The bigger point: raw ergot is toxic and should never be taken as a supplement at all. If you're managing Rett syndrome with Daybue, please run any herbal product past your pharmacist or doctor first.

References
  1. Eadie MJ. Convulsive ergotism: epidemics of the serotonin syndrome? Lancet Neurol 2003;2:429-34. PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Ergot Also Interacts With Other Medications

Ergot has 461 moderate known drug interactions in our database — the Trofinetide one above is one of them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Ergot

Covers the 2,830 medications we’ve checked against Ergot. Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Trofinetide

This page covers Ergot only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Trofinetide page lists 30 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Adrafinil (moderate), Cannabidiol (cbd) (moderate), Cannabinol (cbn) (moderate) and Cannabis (moderate).

By severity: 1 major · 19 moderate · 10 minor.

From our pharmacist’s overview on the Trofinetide page

“Families managing Rett syndrome often add supplements alongside trofinetide (Daybue), and this is a list that deserves real care rather than a quick skim. The interactions fall into two patterns.”

Reviewed by 2 · Jul 18, 2026

Open the Trofinetide interaction page

How much people look this up

Where Ergot and Trofinetide Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Ergot
Steady interest

#788 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Trofinetide
Steady interest

#2,404 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Ergot

What is Ergot?

Ergot
  • Heavy menstrual or uterine bleeding
  • Bleeding after childbirth
  • Migraine headaches
  • Stimulating uterine contractions

Ergot is a toxic fungus that grows on rye and contains powerful chemicals (ergot alkaloids) that strongly narrow blood vessels and squeeze the uterus. Because raw ergot is poisonous and the dose is impossible to control safely, it should never be used as a home remedy or supplement. Some purified ergot chemicals are used as prescription drugs under strict medical supervision, but the crude herb is not safe to take.

Read the full Ergot monograph & all interactions
Medication

About Trofinetide

What Is Trofinetide Used For?

Brand name: Daybue

Daybue and Daybue Stix are both approved to treat Rett syndrome in adults and pediatric patients 2 years of age and older. Rett syndrome is a rare neurological condition, and these are the branded forms of trofinetide available to treat it.

Both Daybue (oral solution) and Daybue Stix (powder that is dissolved to make an oral solution) carry this same indication. The safety and effectiveness in children under 2 years of age have not been established.

See full Trofinetide drug information
Keep checking

Other Drugs & Ergot

Browse every other medication we’ve checked against Ergot — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
461Moderate
0Minor
2,368No known interaction
Moderate

461 interactions

Showing 60 of 461 moderate interactions — see all 461 on the Ergot page.

No interaction 2,368 drugs checked — show the list
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

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Pharmacist Counseling Corner

Taking Ergot and Trofinetide Together: Common Questions

Can you take Ergot with Trofinetide?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Ergot and Trofinetide interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.